-The neurochemical and behavioral effects of repeated subdermal administration of methyl parathion (MP) at low doses were investigated. Adult male rats were treated repeatedly with either vehicle or MP subcutaneously (3 mg/kg/day) and observed for the signs of toxicity during the treatment period. The toxic sign, tremor, reached maximum right after 9 th injection in MP-treated rats, and declined thereafter. Animals were sacrificed and brains were taken 1 week or 3 weeks after the daily treatment for measurement of acetylcholinesterase (AChE) 3 H]AF-DX384 binding (6 ~ 38%) in different brain regions, including striatum, hippocampus, frontal cortex, thalamus and midbrain. After 1 week of treatment, the inhibition of AChE in brain regions was from 54 to 74%, whereas receptor densities were only marginally affected in a few regions. The timing of the changes in receptor population correlates well with the changes in behaviors during the repeated MP exposure. Our findings suggest that down-regulation of muscarinic receptors plays a role in the development of tolerance to MP. And, the regulations of muscarinic receptors were different among receptor subtypes and brain regions.